Nowadays, tyrosinase inhibitors are gradually gaining importance in medicine, cosmetics and food industries. Several natural or synthetic tyrosinase inhibitors have been discovered. However, a few of them can be used as skin bleaching agents due to the toxicity problems. The most important skin bleaching agents are hydroquinone, hydroquinone manomethyl ether, arbutin, kojic acid and azelaic acid. Use of hydroquinone in skin bleacher cosmetics is prohibited because of its clinical side effects, and use of less toxic derivatives thereof is preferred. Only a few antimelanogenic agents such as kojic acid and arbutin are commercially available in the market
Kojic acid has antibacterial and antifungal properties, which inhibits catecholase activity of tyrosinase that is an essential rate-limiting enzyme in biosynthesis of melanin pigment which gives skin its color. Therefore, it is contained in dermocosmetics/cosmeceutics for depigmentation after sunburn and in the treatment of hyperpigmentation in the cosmetic industry in order to prevent enzymatic darkening, for its skin bleaching effect. The presence of kojic acid in cosmetic products inhibits tyrosinase enzyme by preventing reuptake of oxygen required for slow and reversible competitive darkening, and it is also known that it forms chelation with active site copper metals, which is effective on the enzyme activity (Chen 1991; Burdock 2001; Kim 2003; Brtko 2004; Bentley 2006). Iron released in the skin due to chronic exposure to the sun rays causes wrinkles. The experiments of kojic acid on hairless rats showed that wrinkles observed on the kojic acid administered rats subjected to UV rays are less than those seen on the skin of the rats not received kojic acid. Furthermore, it is also used in the food and cosmetic industry in order to increase shelf life, due to its protective effect against physical and chemical degradation. In order to prevent spot formation resulting from storage and processing of colored food products, kojic acid also finds application as an anti-spot due to its tyrosinase inhibitory feature (Uchino 1988).
In recent years, in order to improve the low stability of kojic acid, ester, tripeptide-amides and aminoacid-amides are synthesized, and an examination made on the antityrosinase activity thereof revealed that their stability is increased to a great extent. This result is based on an increase in hydrophobic interactions between the synthesized compounds and tyrosinase active site (Noh 2007; Noh 2009; Kim 2003; Kim 2004). In the subsequent studies, metal complexes of these derivatives with strong antityrosinase effect are prepared in order to solve the problem of low cellular permeability (Kwak 2010). In another study, tyrosinase inhibitory activity is examined, wherein kojic acid derivatives are obtained by joining pyrone cores of two kojic acid molecules through an ethylene linkage, which are 8 times more active than kojic acid (Lee 2006). In kojyl thioether derivatives, tyrosinase inhibitory activity is also increased by appropriate lipophilic alkyl chains (Rho 2010), and in ester derivatives, compounds are synthesized which are more effective than the kojic acid (Rho 2011). Moreover, complexes of kojic acid derivatives in the form of mannic base with ruthenium metal are prepared, to obtain anticancer activity (Kasser 2010). Currently, use of kojic acid in pharmaceutical products is not approved by the FDA. In a research on current use concentrations conducted by Personal Care Products Council, it is observed that kojic acid is used at a concentration of 0.1-2%, with the highest concentration being used in face and neck creams, lotions and powders.
An article titled “Synthesis and Evaluation of Anticonvulsant and Antimicrobial Activities of 3-Hydroxy-6-methyl-2-substituted 4W-Pyran-4-one Derivatives” discloses the compounds synthesized from kojic acid, and having the chemical formula given below. Herein, it is determined that a compound, wherein R is a benzyl, does not exhibit anticonvulsant and antifungal activity.

In another study, 3-hydroxy-6-hydroxymethyl-2-substituted 4H-pyran-4-one derivatives are synthesized and their anticonvulsant activity is examined (Aytemir et al., Arzneimittelforschung 2010; 60(1):22-29).
Since kojic acid exhibits high toxicity against ceils and low stability against water and oxygen, it has a limited application area. Furthermore, kojic acid and some derivatives thereof are low soluble in oil and unstable at high temperature for long-term storage. This directly prevents use of those substances in oil-containing cosmetic and skin care products. For kojic acid used as a skin bleacher, skin lightener and depigmentation agent in cosmetic products, ester derivatives such as kojic dipalmitate and kojic isopaimitate are present in the marketed products as a cosmetic ingredient. Therefore, it has become important to obtain more reliable new derivatives of kojic acid, in order to improve physical properties and biological activities thereof and enhance its industrial application area. Moreover, kojic acid that is allowed to be used at only low doses due to its toxic effects on thyroid gland has low permeability and stability problems. Therefore, more efficacious and safe products should be developed. Due to their damage on both medical and leather and textile sectors, dermatophytes are fungi that cause great economical damages. Today, there is a need for new antifungal agents since antifungal drugs are used in the treatment of dermatophytes that settle on skin, hair and nails where they cause common infections, and fungi rapidly develop resistance to existing drugs. Mycobacterium avium subsp. paratubervuiosis is a pathogen which causes paratuberculosis in milk cows, i.e. Johne disease, and which is also linked to Crohn disease in humans. It is abundant in nature, soil and water. It is also commonly available in household dust and plants. Mycobacterium avium complex (MAC) is the cause of pulmonary diseases in AIDS patients. It is a disease cause in animals and humans, it is a factor responsible for contamination of water. It is spread by ingestion of contaminated water and foods. New treatment methods have been developed by preparing combinations of commercially available antibiotics, but new antibiotics could not be developed which have antimycobacterial effect.